Current Respiratory Medicine Reviews

Joseph Varon  
The University of Texas Health Science Center
Houston, TX
USA

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Role of Prostaglandin (PG) and Peroxisome Proliferator-Activated Gamma (PPAR γ ) in Pulmonary Fibrosis

Author(s): Izumi Hayashi, Hirahito Endo, Masato Katagiri, Hidero Kitasato.

Abstract:

Pulmonary fibrosis is involved in several respiratory diseases such as idiopathic interstitial pneumonias, druginduced pulmonary disease, occupational or environmental pulmonary disease and collagen vascular disease, and leads to systemic fatal damage in some cases. Several cytokines, inflammatory mediators, and growth factors play a complicated role in the progression of fibrosis, resulting in difficulty in specific therapy to overcome the disease. Among those mediators, inducible cyclooxygenase (COX)-2-dependent prostaglandin (PG) E2 exhibits inhibitory effects for fibroblast proliferation and collagen synthesis. Induction of COX-2 expression associated with increased production of PGE2 was observed in bleomycin-induced pulmonary fibrosis in rat. The inhibitory effects could be mediated via the EP2 and/or EP4 receptors coupled to elevation of cAMP. Fifteen-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), which is a derivative of PGD2 by non-enzymatic hydrolysis and an anti-inflammatory PPAR γ ligand, has been focused in asthma, chronic obstructive pulmonary disease, acute lung injury and pulmonary fibrosis. Attenuation of pulmonary fibrosis by 15d-PGJ2 has confirmed by introduction of cells retrovirally transfected with PGD2 synthase cDNA. Administration of PGD2 synthaseexpressing cells to mice suppressed the fibrosis with reduced expression of fibrogenic growth factors. Thus, manipulation of anti-fibrogenic prostaglandins, PGE2 and 15d-PGJ2 may contribute to the development of specific therapy for pulmonary fibrosis.

Keywords: Pulmonary fibrosis, interstitial pneumonia, prostaglandin E2, 15-deoxy-Δ12,14-prostaglandin J2, prostaglandin D2 synthase, PPAR γ

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Article Details

VOLUME: 5
ISSUE: 1
Year: 2009
Page: [3 - 5]
Pages: 3
DOI: 10.2174/157339809787354074